Enteric microbiome markers as early predictors of clinical outcome in allogeneic hematopoietic stem cell transplant (allo-HSCT): results of a prospective study in adult patients

Background Infections and graft-versus-host disease (GvHD) still represent major, not easily predictable, complications in allogeneic hematopoietic stem cell transplant (allo-HSCT). Both conditions have been correlated to altered enteric microbiome profiles during the peri-transplant period. The main objective of this study was to identify possible early microbiome-based markers useful in pre-transplant risk stratification. Methods Stool samples were collected from 96 consecutive patients at the beginning of the pre-transplant conditioning regimen (T0), ten (T1), and thirty (T2) days following transplant. When significant in univariate analysis, the identified microbiome markers were used in multivariate regression analyses together with other significant clinical variables for allo-HSCT-related risk stratification. Four main outcomes were addressed: (i) septic complications, (ii) GvHD, (iii) relapse of the underlying disease and (iiii) mortality. Results The presence of >5% proinflammatory Enterobacteriaceae at T0 was the only significant marker for the risk of microbiologically confirmed sepsis. Moreover, ≤10% Lachnospiraceae at T0 was the only significant factor for increased risk of overall mortality, including death from both infectious and non-infectious causes. Finally, a low bacterial alpha-diversity (Shannon index ≤1.3) at T1 was the only variable significantly correlating with an increased risk of GvHD within 30 days. Conclusions Microbiome markers can be useful in the very early identification of patients at risk for major transplant-related complications, offering new tools for individualized pre-emptive or therapeutic strategies to improve allo-HSCT outcomes.